Of more than 175 ectodermal dysplasias affecting skin and skin appendages, the X-linked anhidrotic ectodermal dysplasia (EDA) is the only one for which the gene involved has been identified. The gene encodes a protein, which we have named ectodysplasin-A, that has a single transmembrane region and a long, extracellular carboxyterminal tail. Because individuals with EDA have sparse hair, rudimentary teeth, and few sweat glands, the gene is likely involved at an early branch point in the interaction of mesenchyme and embryonic ectoderm during the development of skin appendages. Work in the last year has analyzed the gene and its transcripts. Analysis of the promoter region has revealed transcription elements that include enhancers, possibly implicated in the tissue specificity of the gene; they include sites that implicate the wnt and EGF pathways. With our collaborators, we had demonstrated that the Tabby mouse, which has many of the features observed in human EDA, results from the loss of function of the orthologous mouse gene. Now a first transgenic mouse, which incorporates one of the 8 isoforms of the protein, partially rescues the Tabby phenotypes. This provides an experimental system to study the gene function systematically during embryonic development.